Trace Amine-Associated Receptor 1 Agonists for Schizophrenia
Why this work is in the frame
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Bibliographic record
Abstract
TAAR1 agonists are an emerging drug class in the treatment of schizophrenia as they may offer a novel mechanism of action for symptom management without blocking dopamine D2 receptors, unlike currently available antipsychotic medications that act primarily via D2 binding. Two TAAR1 agonists are currently in clinical development for schizophrenia. The first is ulotaront, a TAAR1 full agonist with 5-hydroxytryptamine 1A agonist activity that is administered orally once daily, and the other is ralmitaront, a TAAR1 partial agonist that is also administered orally once daily. The published clinical trial evidence on TAAR1 agonists currently only pertains to ulotaront, which includes a 4-week, phase II, placebo-controlled randomized trial on patients with acute exacerbation of schizophrenia and a 26-week, open-label extension study of this same trial. These studies demonstrated improvements across disease-specific and global impression scales following treatment with ulotaront, with statistically significant differences compared to placebo, and no increased risk of the side effects (extrapyramidal symptoms and metabolic changes) associated with traditional D2-binding antipsychotic therapies. There is currently no cost information available for TAAR1 agonists. Ulotaront is currently undergoing phase III trials and, though it is not currently approved in any country and the date of Health Canada licensing and marketing in Canada is not yet known, it is expected to be the first TAAR1 agonist for schizophrenia in the Canadian market. Ulotaront received Breakthrough Therapy designation from the FDA in 2019 to expedite its development and the drug’s manufacturer is planning to file a New Drug Application with the FDA in 2023. Ralmitaront is currently in phase II trials, which are expected to be completed in 2023.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it